Renal tissue (slices of renal cortex or separated renal tubular cells) is incubated with selected nephrotoxicants in sealed flasks containing a nutritional, physiological medium. Biochemical and physiological processes directly involved in the normal functioning of renal tubular cells are monitored to elucidate the effects of the toxicants on the cells. By altering the composition of the medium (e.g., pH, pCO2, cofactor concentrations) and the physiological status of the cells (e.g., glutathione-depleted, microsomal enzyme-induced), the same system is used to study the biochemical/molecular mechanisms of chemical nephropathy and the metabolism of the toxicants by the kidney. Correlative studies are conducted with intact animals to determine the roles of non-renal factors (e.g., toxicant distribution, non-renal toxicant metabolism, extrarenal organ damage) in the pathophysiology of the kidney injury.